The ever-mutating flu virus is notoriously difficult to protect against as the efficacy of yearly flu vaccinations are contingent on the strain of virus circulating once the season arrives. Publishing their work in Cell, researchers from Rockefeller University have suggested that a previously unknown mechanism within the immune system could be harnessed to create a more effective and efficient vaccine for the flu virus.
Senior Study Author Jeffrey Ravetch, head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology, said: “While the conventional flu vaccine protects only against specific strains, usually three of them, our experiments show that by including modified antibodies within the vaccine it may be possible to elicit broad protection against many strains simultaneously.
“We believe these results may represent a preliminary step toward a universal flu vaccine, one that is effective against a broad range of the flu viruses.”
The researchers honed in on antigens, immune proteins that target specific foreign proteins, where an antibody latches on to an antigen and the other end, called the Fc region, binds to immune cells and so helps coordinate the immune response.
As the flu virus mutates across so many different strains, conventional vaccines can often be ineffective which has led to the idea of a universal flu vaccine as something of a “holy grail” and the research team believed that they have pointed the way with their chemical modifications to the Fc region of antibodies. These regions go on to form complexes with vaccine antigens, which then modulate the evolving vaccine response.
The team teased out how this chemical modification improved the immune response, the researchers used cell cultures and mice to study the effects of sialylated Fc regions binding to B cells. By binding to specific protein receptors in an effect which triggers a process whereby the Fc region establishes a high threshold for the immune response, so that only B cells producing the highest affinity antibodies are activated.
Jad Maamary, a colleague working in Ravetch’s lab, explained: “When we immunised mice with just the H1 protein from one strain or with the sialylated complexes containing the same viral protein, we found both offered the same strain of flu. However, when we exposed them to strains expressing different versions of the H1 protein, only the sialylated immunisations offered protection. This was no small accomplishment, because H1 viruses can vary significantly from one another.”
Another colleague, Taia Wang, added: “The new mechanism we have uncovered, by which a vaccine containing sialylated antibodies elicits broadly protective antibodies, could potentially be harnessed to reduce the tremendous morbidity and mortality caused by seasonal influenza virus infections. We are now looking into applying this strategy toward improving existing vaccines; ideally, this would result in a vaccine that provides life-long immunity against flu infections.”